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Preservation of thalamocortical projections to the sensorimotor cortex is related to improved hand function in children with cerebral palsy (CP). Whether CP is associated with altered microstructure of these sensorimotor projections or other thalamocortical pathways remains unclear. Forty-two children with congenital hemiplegia and fifteen typically developing children (TDC) underwent structural and diffusion-weighted imaging (high-angular-resolution diffusion imaging) using a 3T MRI. Structural T1-images were parcellated into 34 cortical regions and the thalamus per hemisphere. Thalamocortical projections were extracted using probabilistic tractography and the top tan cortical regions with the greatest number of thalamocortical streamlines for the TDC group were selected for further analysis. The thalamus was parcellated based on its cortical connections. Differences between hemispheres for thalamocortical streamline numbers to each cortical region [asymmetry index (AI)], tract volume and tract microstructure [weighted mean fractional anisotropy (FA) and mean diffusivity (MD)] were calculated. Correlations between these measures (AI, FA and MD) and sensorimotor function were performed. Thalamocortical projections showed topographical organisation based on cortical connectivity. Projections to paracentral lobule, pre-central and post-central gyri showed greater AI in CP group, which indicates reduced streamlines on the ipsilesioned hemisphere. Reduced FA, reduced tract volume and increased MD were also found for these thalamocortical projections on the ipsilesioned hemisphere in children with CP. Changes in AI and tract microstructure of these projections were associated with poorer sensorimotor function. The findings suggest CP is associated with reorganisation of thalamocortical projections to the sensorimotor cortex. Integrity in these projections may underpin deficits in sensorimotor function. [ABSTRACT FROM AUTHOR]

Combinatorial expression of transcription factors forms transcriptional codes to confer neuronal identities and connectivity. However, how these intrinsic factors orchestrate the spatiotemporal expression of guidance molecules to dictate the responsiveness of axons to guidance cues is less understood. Thalamocortical axons (TCAs) represent the major input to the neocortex and modulate cognitive functions, consciousness and alertness. TCAs travel a long distance and make multiple target choices en route to the cortex. The homeodomain transcription factor Gbx2 is essential for TCA development, as loss of Gbx2 abolishes TCAs in mice. Using a novel TCA-specific reporter, we have discovered that thalamic axons are mostly misrouted to the ventral midbrain and dorsal midline of the diencephalon in Gbx2-deficient mice. Furthermore, conditionally deleting Gbx2 at different embryonic stages has revealed a sustained role of Gbx2 in regulating TCA navigation and targeting. Using explant culture and mosaic analyses, we demonstrate that Gbx2 controls the intrinsic responsiveness of TCAs to guidance cues. The guidance defects of Gbx2-deficient TCAs are associated with abnormal expression of guidance receptors Robo1 and Robo2. Finally, we demonstrate that Gbx2 controls Robo expression by regulating LIM-domain transcription factors through three different mechanisms: Gbx2 and Lhx2 compete for binding to the Lmo3 promoter and exert opposing effects on its transcription; repressing Lmo3 by Gbx2 is essential for Lhx2 activity to induce Robo2; and Gbx2 represses Lhx9 transcription, which in turn induces Robo1. Our findings illustrate the transcriptional control of differential expression of Robo1 and Robo2, which may play an important role in establishing the topography of TCAs. [ABSTRACT FROM AUTHOR]

Thalamocortical axons must cross a complex cellular terrain through the developing forebrain, and this terrain has to be understood for us to learn how thalamocortical axons reach their destinations. Selective fasciculation, guidepost cells and various diencephalic and telencephalic gradients have been implicated in thalamocortical guidance. As our understanding of the relevant forebrain patterns has increased, so has our knowledge of the guidance mechanisms. Our aim here is to review recent observations of cellular and molecular mechanisms related to: the growth of thalamofugal projections to the ventral telencephalon, thalamic axon avoidance of the hypothalamus and extension into the telencephalon to form the internal capsule, the crossing of the pallial-subpallial boundary, and the growth towards the cerebral cortex. We shall review current theories for the explanation of the maintenance and alteration of topographic order in the thalamocortical projections to the cortex. It is now increasingly clear that several mechanisms are involved at different stages of thalamocortical development, and each contributes substantially to the eventual outcome. Revealing the molecular and cellular mechanisms can help to link specific genes to details of actual developmental mechanisms. [ABSTRACT FROM AUTHOR]

Sleep spindles are generated in thalamocortical circuits. Thalamocortical projections can be classified as one of two main types: a “core” network consisting of spatially concentrated projections terminating in cortical layer IV, and a “matrix” network with more diffuse projections, terminating in the superficial cortical layers. It has been hypothesized that sleep spindles can be generated in both systems, but localized spindles are preferentially generated in the “core” system and global spindles in the “matrix system”. Our analysis of laminar microelectrode recordings during ECoG spindles indeed reveals that current source density (CSD) is maximal in layer I-II and IV, consistent with the anatomy of the hypothesized “core” and “matrix” networks. However, CSD is prominent at both depths in both local and global spindles, and CSD magnitude is strongly correlated between superficial layers and layer IV (although less so in local spindles). Fast spindles slow relatively greater CSD in layer IV and slow spindles in superficial layers. Sleep spindles are associated with several neurobehavioral markers, such as memory consolidation, cognitive ability and disease phenotypes. These associations, however, were mainly found with fast spindles. Centroparietal fast spindles also appear more prominently in EEG recordings and leave more prominent spectral peaks. While neither slow nor fast spindles rely exclusively on both “core” and “matrix” thalamocortical projections, it is likely that spatially focused “core” projections to layer IV are especially significant for sleep spindle function due to their role in fast spindle generation. [ABSTRACT FROM AUTHOR]